The field of the invention is a system for detection and treatment of cancer.
Currently, existing methods of diagnosing prostate cancer involve a series of steps and procedures; see Petrylak, infra; Potter,et al., infra; Naitoh, et al., infra; Hegarty et al., infra; Selley, et al., infra. The initial detection of signs that the patient may have prostate cancer is most commonly the result of some regular form of check-up carried out by a primary care physician, which includes a digital rectal examination. In this examination the physician inserts his finger into the rectum in order to be able to feel the size, shape, and texture of the prostate and other nearby organs. Although a highly experienced physician can make a relatively good diagnosis using digital rectal examinations (xe2x80x9cDRExe2x80x9d), it is a xe2x80x9csubjectivexe2x80x9d technique. The problem with using DREs to make decisions about what to do with particular patients is that two different experienced physicians may think that they feel quite different things when they carry out a DRE on the same patient. Neither of these physicians is necessarily right or wrong in what they think. They cannot see what they are feeling and they are doing their best to make wise decisions. Since the mid 1980""s, prostate cancer diagnosis is performed by prostate specific antigen (xe2x80x9cPSAxe2x80x9d) tests. The PSA test has revolutionized the detection of prostate cancer and monitoring of the effects of treatment. On its own, it is very probably responsible for the accurate diagnosis of prostate cancer in millions of men worldwide.
A PSA test measures the level of prostate specific antigen in the patient""s blood. Using the most common type of PSA test currently available in the United States, the average, normal, healthy, 50-year-old male is generally believed to have a PSA of less than 4.0 nanograms per milliliter of blood (4.0 ng/ml). An elevated PSA level in blood may be associated with prostate cancer. Several modified versions of PSA tests can be performed to increase the reliability of the diagnosis. Although PSA tests have revolutionized prostate cancer diagnosis, it is not an absolute test of prostate cancer. Typically if both DRE and PSA tests are positive, a biopsy is taken. The biopsies of the prostate are carried out under ultrasound guidance. In this method, several samples of tissue are taken from the prostate using a method normally called sextant biopsy. In carrying out the actual biopsy, the biopsy needle is inserted into the prostate to take six or more samples of tissue from the prostate. The precise number of samples taken depends upon what the urologist is able to see using the ultrasound machine. This procedure is painful, uncomfortable, and may lead to bleeding complications.
Available methods of treatment for prostate cancer include hormone therapy, surgery, radiation therapy and cryotherapy; see Potter, et al., infra; Naitoh, et al., infra; Hegarty et al., infra; Selley, et al., infra. Hormone therapy is primarily used to treat patients who have prostate cancer that is not confined to the prostate. The intent of hormone therapy is first, to delay the progression of the cancer, and second, to increase the patient""s survival while simultaneously maximizing his quality of life. Hormone therapy is limited by significant side effects.
The next available method of treatment for prostate cancer is surgical treatment, and is most common among younger, healthy patients, whose tumors are believed to be confined to the prostate (i.e., stages T1 or T2). There are two basic forms of surgery for removal of the prostate: radical retropubic prostatectomy and radical perineal prostatectomy. The only difference between these two techniques that is of importance to the patient, is that the surgeon uses different routes to reach the prostate. In radical retropubic prostatectomy the surgeon cuts down to the prostate through the lower abdomen. In a radical perineal prostatectomy, the surgeon cuts up to the prostate between the anus and the scrotum. All forms of surgery for removal of the prostate are associated with complications. These include lack of bladder control (urinary incontinence), urethra stricture (difficulty in urination), impotence, and the normal risks associated with anesthesia and major surgical procedures. There is general agreement that lower complication rates are usually found among those surgeons who carry out a significant number of prostatectomies on a regular basis. In other words, practice makes the surgeon more competent. However, even the best surgeons have patients with unexpected complications. Any form of prostatectomy is a major operation and has risks attached.
The third method for treatment of prostate cancer is radiation therapy. Radiation therapy is intended to treat the prostate cancer that is confined to the prostate and/or the surrounding tissues (i.e., clinical stages T1, T2, and T3). Radiation therapy is delivered using an external beam of x-rays carefully directed to the areas of the pelvis that include the prostate. Other forms of radiation therapy are xe2x80x9cinterstitial brachytherapyxe2x80x9d (commonly known as seed implantation), in which the radiation oncologist and a surgeon implant radioactive pellets or xe2x80x9cseedsxe2x80x9d into the prostate, and those pellets radiate the prostate and the surrounding tissue over time. It is not uncommon for brachytherapy and external beam radiation therapy to be used in combination in appropriate patients. Like surgery, all forms of radiation therapy are associated with complications, including acute cystitis, proctitis, and enteritis. In addition, most series of radiotherapy patients have been associated with some subsequent urinary and sexual dysfunction.
Finally, cryotherapy is a means of treatment for prostate cancer. Cryotherapy is an old technique that has been reborn as a result of advances in technical capability. Rather than removing the prostate (as in conventional surgery) or using radiation therapy with different forms of x-rays, cryotherapy is a method of freezing the prostate and other appropriate nearby tissues to extremely low temperatures with liquid nitrogen. This technique is designed to kill all the prostate cancer tissue without having to take the risks involved in carrying out invasive surgery. The known side effects of cryotherapy can include impotence (in about 80% of patients), scarring of the urethra and urinary dysfunction (which are relatively unusual), and irritation of the bladder, the urethra, the rectal wall, and the genitalia. This last group of side effects can include pain on urination, a burning sensation during urination, frequent and unexpected urination, blood in the urine (hematuria), and swelling of the penis or the scrotum.
Thus, existing methods of diagnostics and treatment for prostate cancer suffer from several limitations. Specifically, the existing methods of diagnostics are invasive and inconvenient. The blood test for PSA is invasive and requires a blood sample. In addition, this method does not acquire a sample directly from the prostate. The existing methods of treatment also suffer from several limitations. Specifically, surgery and hormone therapy result in severe side effects. In addition, chemotherapy is limited by severe side effects of cytotoxic agents.
The present invention offers a device and method for performing a diagnostic test and/or treating disease, illustrated herein by cancer, that is an advantageous alternative to the existing methods of diagnostics and treatment. The device comprises is an ultrasound transducer and a reservoir connected to the transducer. The reservoir is in the form of a cartridge that is shaped to be placeable against the tissue in the region of the disease to be diagnosed or treated, e.g., at the site of a cancerous tumor such as prostate gland tissue, and contains a coupling medium to transmit unltrasound to the tissue whereby to produce cavitation for permeabilizing the tissue. The coupling medium can contain a cavitation enhancer. The method is illustrated with respect to the diagnosis and treatment of prostate cancer but is applicable to other forms of tumors, or other diseases that are accessible to a probe, such as pancreatic tumors, skin tumors, colon tumors, and cervical tumors.
In the case of diagnostics, the present invention uses ultrasound to extract a marker, such as a cancer tumor marker, into the coupling medium and provides advantages over existing methods: i) it is non-invasive with tumors in accessible locations, such the prostate gland, colon, or cervix; ii) it measures a marker associated with interstitial fluid associated with the tumor, e.g., PSA concentration in the interstitial fluid of the prostate, as opposed to systemic levels, which provides in increased diagnostic sensitivity; and iii) it is convenient to use.
In the case of treatment, the present invention uses ultrasound to deliver one or more drugs from the coupling medium directly to the site of the disease and provides advantages over existing methods: i) it is non-invasive with disease sites in accessible locations, as above; ii) it delivers drugs locally to the site, thus limiting side effects; and iii) it is painless.
In particular, the present invention consists of the following major components: i) an ultrasound transducer probe placed in contact with the body; ii) a power source to activate the ultrasound probe; iii) a reservoir attached to the transducer to collect extracted markers or to hold the drugs to be delivered; and iv), for diagnostic procedures, a detection method to measure the concentration of extracted markers.